The brain defines us. Therefore, unlike other organ systems in the body, the study of human brain tissue is largely confined to samples donated after death. What can we learn about psychiatric illness from post-mortem samples? In this talk, I’ll overview the use of transcriptional profiling to characterize alterations in brain molecular networks in tissue from subjects with psychiatric disorder. I will also discuss the challenges inherent in the interpretation of data derived from post-mortem samples, and several of our ongoing projects that use a convergence of transcriptional profiling data from animal models to disambiguate results.